As is well known, polymers are molecules containing one or more chains, which contain multiple copies of one or more constitutional units. An example of a common polymer is polyisobutylene,
where n is an integer, typically an integer of 10 or more, more typically on the order of 10's, 100's, 1000's or even more, in which the constitutional units in the chain correspond to isobutylene monomers:
(i.e., they originate from, or have the appearance of originating from, the polymerization of isobutylene monomers, in this case the addition polymerization of isobutylene monomers). Copolymers are polymers that contain at least two dissimilar constitutional units.
Numerous polymer-based medical devices have been developed for the delivery of therapeutic agents to the body. In accordance with some typical delivery strategies, a therapeutic agent is provided within a polymeric carrier layer and/or beneath a polymeric barrier layer that is associated with a medical device. Once the medical device is placed at the desired location within a patient, the therapeutic agent is released from the medical device at a rate that is dependent upon the nature of the polymeric carrier and/or barrier layer.
Materials which are suitable for use in making implantable or insertable medical devices typically exhibit one or more of the qualities of exceptional biocompatibility, extrudability, elasticity, moldability, good fiber forming properties, tensile strength, durability, and the like. Moreover, the physical and chemical characteristics of the device materials can play an important role in determining the final release rate of the therapeutic agent.
As a specific example, block copolymers of polyisobutylene and polystyrene, for example, polystyrene-polyisobutylene-polystyrene triblock copolymers (SIBS copolymers), which are described in U.S. Pat. No. 6,545,097 to Pinchuk et al., which is hereby incorporated by reference in its entirety, have proven valuable as release polymers in implantable or insertable drug-releasing medical devices. As described in Pinchuk et al., the release profile characteristics of therapeutic agents such as paclitaxel from SIBS copolymer systems demonstrate that these copolymers are effective drug delivery systems for providing therapeutic agents to sites in vivo.
These copolymers are particularly useful for medical device applications because of their excellent strength, biostability and biocompatibility, particularly within the vasculature. For example, SIBS copolymers exhibit high tensile strength, which frequently ranges from 2,000 to 4,000 psi or more, and resist cracking and other forms of degradation under typical in vivo conditions. Biocompatibility, including vascular compatibility, of these materials has been demonstrated by their tendency to provoke minimal adverse tissue reactions (e.g., as measured by reduced macrophage activity). In addition, these polymers are generally hemocompatible as demonstrated by their ability to minimize thrombotic occlusion of small vessels when applied as a coating on coronary stents. Furthermore, these polymers possess many interesting physical and chemical properties sought after in medical devices, due to the combination of polymer blocks.
Although polymers are known for use in drug-releasing medical devices, there is a continuing need for novel polymeric materials that can serve as release layers in medical devices. In particular, it may be advantageous to provide polymers that, in addition to the biocompatibility, biostability, and physical and chemical properties of known block polymers such as SIBS, provide enhanced drug release characteristics from the release layer such as a linear and sustained release of the therapeutic agent instead of a burst release profile seen in prior art SIBS block copolymers.